Third International Workshop on HIV and Women, January 14-15, 2013, Toronto

Mark Mascolini

A multistudy review of HIV-discordant heterosexual couples estimated an HIV transmission rate of 0.0 to 0.14 per 100 person-years when the positive partner has an undetectable viral load thanks to antiretroviral therapy [1]. Two separate analyses pooled data from three or six studies, including HPTN 052, the randomized trial that found a 96% lower transmission risk with immediate versus deferred antiretroviral therapy in discordant couples with an initial CD4 count between 350 and 550 [2].

Despite strong evidence in HPTN 052 that viral suppression greatly limits HIV transmission risk in steady couples, research has not established transmission risk between HIV-discordant partners when the positive partner has a viral load too low to measure. To address that question, Canadian researchers planned a systematic review and meta-analysis of studies published through January 2012 that reported (1) HIV transmission rates, (2) antiretroviral treatment history, and (3) viral load of the HIV-positive partner.

The researchers tracked down 17,408 citations, only three of which met all eligibility criteria, including confirmed full virologic suppression in the HIV-positive partner. Three additional studies (including HPTN 052) met the first two eligibility criteria but had unconfirmed viral suppression data.

The three studies that met all eligibility criteria included 991 heterosexual couples with 2064 person-years of follow-up. Results of these three studies yielded a pooled HIV transmission rate of 0.0 per 100 person-years (95% confidence interval 0 to 0.5). In other words, if 100 discordant heterosexual couples whose positive partner had an undetectable viral load had sex for 1 year, the HIV transmission rate would be 0, or at most vanishingly small.

Next the researchers added the three studies that had data on transmission rates and antiretroviral history but not confirmed viral suppression. Two observational studies added 3470 couples, while HPTN 052 added 1763. In the resulting six-study analysis, the pooled transmission risk was 0.14 per 100 person-years (95% confidence interval 0.04 to 0.31). That result means that if 1000 discordant heterosexual couples whose positive partner had an undetectable viral load had sex for 1 year, there would be between 1 and 2 HIV transmissions.

The six studies analyzed included 4 HIV transmissions. All 4 transmissions occurred within the 6 months after the HIV-positive partner started antiretroviral therapy and so still may have had a detectable viral load. When the researchers reran their analysis after eliminating these 4 transmissions, the risk of HIV transmission was 0.0 per 100 person-years (95% confidence interval 0.0 to 0.1).

The researchers noted that their analysis has several limitations. It did not (1) include same-sex couples, (2) discriminate between vaginal and anal sex, (3) establish how often couples had sex, (4) establish the direction of HIV transmission, (4) establish the exact viral load at the time of transmission, (5) account for sexually transmitted infections, or (6) determine the extent of condom use.

The investigators conclude that "there is a minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has an undetectable viral load" while taking combination antiretroviral therapy. They believe their findings can inform fertility counseling and sexual health counseling for HIV-positive women.